chr9-105309857-C-A

Position:

• chr9-105309857-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_080546.5(SLC44A1):​c.260C>A​(p.Thr87Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,460,964 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC44A1 NM_080546.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.29

Genes affected

SLC44A1 (HGNC:18798): (solute carrier family 44 member 1) Enables choline transmembrane transporter activity. Involved in choline transport and transmembrane transport. Located in several cellular components, including cytosol; mitochondrion; and nucleoplasm. Implicated in high grade glioma. [provided by Alliance of Genome Resources, Apr 2022]

SLC44A1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC44A1	NM_080546.5	c.260C>A	p.Thr87Asn	missense_variant	3/16	ENST00000374720.8	NP_536856.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC44A1	ENST00000374720.8	c.260C>A	p.Thr87Asn	missense_variant	3/16	1	NM_080546.5	ENSP00000363852.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1460964 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726784

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 13, 2024

The c.260C>A (p.T87N) alteration is located in exon 3 (coding exon 3) of the SLC44A1 gene. This alteration results from a C to A substitution at nucleotide position 260, causing the threonine (T) at amino acid position 87 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	.;T;.
Eigen	Benign	0.082
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.71	D;D;D
MetaSVM	Uncertain	0.022	D
MutationAssessor	Pathogenic	3.1	M;M;M
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.0	D;D;D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0040	D;D;D
Sift4G	Uncertain	0.015	D;D;D
Polyphen		0.94	P;B;.
Vest4		0.77
MutPred		0.30		Loss of phosphorylation at T87 (P = 0.0694);Loss of phosphorylation at T87 (P = 0.0694);Loss of phosphorylation at T87 (P = 0.0694);
MVP		0.71
MPC		0.55
ClinPred		0.98	D
GERP RS		5.0
Varity_R		0.31
gMVP		0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-108072138;